A Phase 3 interventional study of Macitentan 10 mg tablet, once daily. in Pulmonary Arterial Hypertension, sponsored by Actelion. Terminated at 51 sites in 19 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2019-04-16.
Sponsored by Actelion (part of Johnson & Johnson) · Phase 3, Interventional, and Treatment
Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of Eisenmenger syndrome.
699 studies on the registry are indexed under Pulmonary Arterial Hypertension; 140 are open to participants now.
This study's enrollment of 217 is above the median of 40 across 477 interventional studies indexed under Pulmonary Arterial Hypertension.
Browse Pulmonary Arterial Hypertension studies →Actelion is the lead sponsor of 143 studies on the registry; 1 is open to participants now.
Of its 28 completed or terminated interventional studies of FDA-regulated products, 25 (89%) have results posted.
First submitted before Actelion became part of Johnson & Johnson.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period).
Exclusion Criteria:
Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to:
Macitentan 10 mg tablet, once daily.
Drug: Macitentan 10 mg tablet, once daily.
Macitentan 10 mg tablet, once daily.
Also known as: Macitentan, ACT-064992
Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12
NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.
Time frame: From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in WHO Functional Class (FC) at Month 6 and 12
Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.
Time frame: From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in Borg Dyspnea Score at Month 6 and 12
The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.
Time frame: From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12
No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)
Time frame: From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.
The study was conducted at 51 sites in 19 countries (geographical regions: Asia-Pacific, Eastern Europe, Latin America, North America and Western Europe).
| Milestone | DB-macitentan | DB-placebo |
|---|---|---|
| Started | 109 | 108 |
| Treated with 10 mg macitentan | 109 | 108 |
| Completed | 92 | 99 |
| Not completed | 17 | 9 |
| Withdrew: Physician decision | 3 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 |
| Withdrew: Death | 5 | 2 |
| Withdrew: Withdrawal by subject | 7 | 7 |
NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.
| meter (m) | DB-macitentan | DB-placebo |
|---|---|---|
| 6MWD at DB study baseline | 370.6 ± 74.1 | 381.6 ± 76.7 |
| 6MWD at Week 16 in DB study | 395.1 ± 88.4 | 399.9 ± 80.6 |
| Change in 6MWD from DB study baseline to Week 16 | 24.4 ± 71.0 | 18.2 ± 53.0 |
| 6MWD at Month 6 in OL study | 396.8 ± 96.5 | 425.0 ± 72.1 |
| Change in 6MWD from DB study baseline to Month 6 | 26.2 ± 77.9 | 43.4 ± 51.5 |
| 6MWD at Month 12 in OL study | 397.1 ± 103.9 | 421.5 ± 76.5 |
| Change in 6MWD from DB study baseline to Month 12 | 26.5 ± 79.8 | 39.9 ± 55.1 |
Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.
| Participants | DB-macitentan | DB-placebo |
|---|---|---|
| WHO functional class I at DB study baseline | 0 | 0 |
| WHO functional class II at DB study baseline | 66 | 65 |
| WHO functional class III at DB study baseline | 43 | 43 |
| WHO functional class IV at DB study baseline | 0 | 0 |
| WHO functional class I at Week 16 in DB study | 3 | 1 |
| WHO functional class II at Week 16 in DB study | 70 | 77 |
| WHO functional class III at Week 16 in DB study | 36 | 30 |
| WHO functional class IV at Week 16 in DB study | 0 | 0 |
| Improvement from DB study baseline to Week 16 | 10 | 15 |
| Worsening from DB study baseline to Week 16 | 0 | 1 |
| WHO functional class I at Month 6 in OL study | 5 | 7 |
| WHO functional class II at Month 6 in OL study | 74 | 79 |
| WHO functional class III at Month 6 in OL study | 28 | 22 |
| WHO functional class IV at Month 6 in OL study | 2 | 0 |
| Improvement from DB study baseline to Month 6 | 19 | 27 |
| Worsening from DB study baseline to Month 6 | 3 | 1 |
| WHO functional class I at Month 12 in OL study | 5 | 7 |
| WHO functional class II at Month 12 in OL study | 74 | 79 |
| WHO functional class III at Month 12 in OL study | 28 | 22 |
| WHO functional class IV at Month 12 in OL study | 2 | 0 |
| Improvement from DB study baseline to Month 12 | 20 | 31 |
| Worsening from DB study baseline to Month 12 | 4 | 3 |
The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.
| score on a scale | DB-macitentan | DB-placebo |
|---|---|---|
| Borg dyspnea score at DB study baseline | 3.0 ± 1.9 | 2.9 ± 1.8 |
| Borg dyspnea score at Week 16 in DB study | 2.7 ± 1.9 | 1.9 ± 1.6 |
| Change from DB study baseline to Week 16 | -0.3 ± 1.4 | -0.2 ± 1.5 |
| Borg dyspnea score at Month 6 in OL study | 2.8 ± 2.0 | 2.5 ± 1.8 |
| Change from DB study baseline to Month 6 | -0.1 ± 2.0 | -0.4 ± 1.5 |
| Borg dyspnea score at Month 12 in OL study | 2.9 ± 2.0 | 2.6 ± 1.9 |
| Change from DB study baseline to Month 12 | -0.1 ± 2.1 | -0.3 ± 1.6 |
No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)
| % of oxygen saturation at rest | DB-macitentan | DB-placebo |
|---|---|---|
| SpO2 at DB study baseline | 84.2 ± 5.6 | 85.4 ± 5.0 |
| SpO2 at Week 16 in DB study | 85.3 ± 5.8 | 85.6 ± 5.4 |
| Change in SpO2 from DB study baseline to Week 16 | 1.1 ± 4.0 | 0.2 ± 4.5 |
| SpO2 at Month 6 in OL study | 85.9 ± 5.9 | 87.4 ± 5.4 |
| Change in SpO2 from DB study baseline to Month 6 | 1.5 ± 4.9 | 2.0 ± 4.3 |
| SpO2 at Month 12 in OL study | 86.4 ± 6.3 | 87.1 ± 5.0 |
| Change in SpO2 from DB study baseline to Month 12 | 2.0 ± 4.4 | 1.6 ± 4.9 |
Collected over From open label study treatment initiation up to 30 days after study treatment discontinuation (max. 24 months + 30 days).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All-enrolled Analysis Set | 7/217 (3.2%) | 62/217 (28.6%) | 152/217 (70%) |
| Event | All-enrolled Analysis Set |
|---|---|
| HaemoptysisRespiratory, thoracic and mediastinal disorders | 9/217 |
| Right ventricular failureCardiac disorders | 6/217 |
| PneumoniaInfections and infestations | 5/217 |
| Pulmonary arterial hypertensionRespiratory, thoracic and mediastinal disorders | 4/217 |
| Cardiac failureCardiac disorders | 3/217 |
| Chest painGeneral disorders | 3/217 |
| PregnancyPregnancy, puerperium and perinatal conditions | 3/217 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 3/217 |
| Brain abscessInfections and infestations | 2/217 |
| Chest discomfortGeneral disorders | 2/217 |
| Event | All-enrolled Analysis Set |
|---|---|
| Upper respiratory tract infectionInfections and infestations | 61/217 |
| HeadacheNervous system disorders | 29/217 |
| HaemoptysisRespiratory, thoracic and mediastinal disorders | 24/217 |
| CoughRespiratory, thoracic and mediastinal disorders | 23/217 |
| Viral upper respiratory tract infectionInfections and infestations | 21/217 |
| BronchitisInfections and infestations | 20/217 |
| Haemoglobin decreasedInvestigations | 20/217 |
| DiarrhoeaGastrointestinal disorders | 18/217 |
| DizzinessNervous system disorders | 18/217 |
| Oedema peripheralGeneral disorders | 14/217 |
| Age, Continuous(years) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Mean | 34.6 (12 to 82) | 34.6 (14 to 62) | 34.6 (12 to 82) |
| Sex: Female, Male(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Female | 77 | 66 | 143 |
| Male | 32 | 42 | 74 |
| Ethnicity (NIH/OMB)(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 89 | 88 | 177 |
| Not Hispanic or Latino | 20 | 20 | 40 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| White | 52 | 51 | 103 |
| Chinese | 35 | 35 | 70 |
| Other Asian | 11 | 11 | 22 |
| Other | 11 | 11 | 22 |
| Region of Enrollment(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Asia-Pacific — Asia-Pacific | 45 | 44 | 89 |
| Asia-Pacific — Eastern Europe | 24 | 26 | 50 |
| Asia-Pacific — Latin America | 18 | 18 | 36 |
| Asia-Pacific — North America | 1 | 4 | 5 |
| Asia-Pacific — Western Europe-Israel | 21 | 16 | 37 |
| Age categorical(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| 12 - 17 years | 12 | 2 | 14 |
| 18 - 55 years | 89 | 99 | 188 |
| ≥ 56 years | 8 | 7 | 15 |
| WHO Functional Class (FC)(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Class I | 0 | 0 | 0 |
| Class II | 66 | 65 | 131 |
| Class III | 43 | 43 | 86 |
| Class IV | 0 | 0 | 0 |
| Downs syndrome status(Participants) | DB-macitentan | DB-placebo | Total |
|---|---|---|---|
| Yes | 10 | 10 | 20 |
| No | 99 | 98 | 197 |
1 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Sep 2013 to primary completion in Jan 2018, 52 months.
Results were first posted in Apr 2019, 1 year 3 months after primary completion.
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Studies of the drug tested here: Macitentan
Pulmonary Arterial Hypertension →